Cannabidiol attenuates seizures and EEG abnormalities in Angelman syndrome model mice
Bin Gu, … , Paul R. Carney, Benjamin D. Philpot
Bin Gu, … , Paul R. Carney, Benjamin D. Philpot
Published September 10, 2019
Citation Information: J Clin Invest. 2019;129(12):5462-5467. https://doi.org/10.1172/JCI130419.
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Concise Communication Neuroscience

Cannabidiol attenuates seizures and EEG abnormalities in Angelman syndrome model mice

Abstract

Angelman syndrome (AS) is a neurodevelopmental disorder characterized by intellectual disability, lack of speech, ataxia, EEG abnormalities, and epilepsy. Seizures in individuals with AS are common, debilitating, and often drug resistant. Thus, there is an unmet need for better treatment options. Cannabidiol (CBD), a major phytocannabinoid constituent of cannabis, has shown antiseizure activity and behavioral benefits in preclinical and clinical studies for some disorders associated with epilepsy, suggesting that the same could be true for AS. Here, we show that acute CBD (100 mg/kg) treatment attenuated hyperthermia- and acoustically induced seizures in a mouse model of AS. However, neither acute CBD nor a 2-week-long course of CBD administered immediately after a kindling protocol could halt the proepileptogenic plasticity observed in AS model mice. CBD had a dose-dependent sedative effect but did not have an impact on motor performance. CBD abrogated the enhanced intracortical local field potential power, including the delta and theta rhythms observed in AS model mice, indicating that CBD administration could also help normalize the EEG deficits observed in individuals with AS. We believe our results provide critical preclinical evidence supporting CBD treatment of seizures and alleviation of EEG abnormalities in AS and will thus help guide the rational development of CBD as a treatment for AS.

Authors

Bin Gu, Manhua Zhu, Madison R. Glass, Marie Rougié, Viktoriya D. Nikolova, Sheryl S. Moy, Paul R. Carney, Benjamin D. Philpot

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Figure 1

CBD attenuates wild running and tonic-clonic seizures induced by acoustic stimuli in AS model mice.

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CBD attenuates wild running and tonic-clonic seizures induced by acousti...
(A) Schematic of the audiogenic seizure paradigm. (B) Treatment (i.p.) with CBD at 100 mg/kg significantly reduced audiogenic seizure frequency. n = 8–16 mice/group. ###P < 0.001 compared with vehicle-treated WT mice; **P < 0.01 compared with vehicle-treated AS mice; Fisher’s exact test. (C) CBD at 100 mg/kg significantly reduced audiogenic seizure severity. Score 0 = no seizure response; score 1 = wild running and jumping; score 2 = tonic-clonic clonus. Data represent the median for individual mice. n = 8–16 mice/group. ###P < 0.001 compared with vehicle-treated WT mice; ***P < 0.001 compared with vehicle-treated AS mice; Kruskal-Wallis test with Dunn’s multiple comparisons test.